The GABAA receptor is the main inhibitory receptor in the CNS. As a result it may be involved in disorders such as anxiety, post-partum depression, epilepsy and alcoholism. The receptor can be modulated by many physiologically and clinically important ligands. These ligands include the neurosteroids allopregnanolone and allotetrahydroxycorticosterone. These two neurosteroids act agonistically; they increase the open time of the channels allowing more current. Other agonistic compounds have been determined to affect the conformation of the receptor. Using SCAM at the TM3 region of the GABAA receptor alpha1 subunit, GABA, diazepam and two different concentrations of propofol were found to change the pattern of water accessible residues in TM3. Diazepam gave a pattern similar to GABA, which may explain how diazepam increases channel opening frequency. Both potentiating and activating propofol concentrations gave different patterns in TM3, which may be related to how propofol affects the open time of channels. Neurosteroids act similarly to propofol on channel open times. Therefore to understand the mechanism of action of neurosteroids, allopregnanolone and allotetrahydroxycorticosterone will be used in a SCAM of the GABAA receptor alpha1 subunit TM3 to determine the conformation induced by the neurosteroids. This conformation will be compared to the ones of propofol, GABA, and BZ to help understand the molecular actions of neurosteroids on the receptor. SCAM will also be done at the TM3 region of the beta1 with GABA and with the neurosteroids. Subunits have flexible structures and may move asymmetrically upon binding of different ligands; therefore, inferring conformations at other subunits may provide additional information on how these ligands cause their actions at the GABAA receptor. The data may provide an understanding to how neurosteroids affect anxiety, depression, sexual behaviors, and susceptibility to alcohol. [unreadable] [unreadable]